Partly with support from the NIH our research team has over the years developed a series of new histofluorescence methods for studies of monoamine transmitters, including the original and several new versions of the formaldehyde and glyoxylic acid methods. Using these methods we have also explored various aspects on the neuroanatomy of, above all, the central noradrenergic and dopaminergic neuron systems. During the present grant period we will, based on very promising findings, engage in the development of a new histofluorescence procedure for highly sensitive visualization of indolamine-containing neurons. This method is based on the very recent findings of a strong catalytic effect of certain metal ions in the histochemical reaction between indolamines (and also catecholamines) and formaldehyde or glyoxylic acid. Our immediate research objectives are (1) to optimize various methodological parameters for sensitive visualization of central serotonin neurons. (2) To study the chemical mechanisms underlying the catalytic effects of magnesium and aluminium ions in the histochemical reactions with monoamines. (3) To initiate, with the aluminium-catalytic method, a systematic study on the organization of serotonin-containing, and other indolamine-containing neurons in the rat CNS. Our preliminary observations show that our new technique is sensitive enough to allow visualization of axons and terminal systems not previously accessible to histofluorescence study, e.g. in cortical areas and in the spinal cord. (4) To continue our studies on the detailed organization and the ontogenetic development of the dopaminergic neuron systems in the brain of rat and man, using the glyoxylic acid method in combination with stereotoxic lesions, HRP-tracing and biochemical analyses. Our studies on the human brain will make use of the relatively unique supply of fetal material from legal abortions that is available in Sweden.